Provided herein are small molecule activators of Nicotinamide Phosphoribosyltransferase (NAMPT), compositions comprising the compounds, and methods of using the compounds and compositions.

The present invention relates to inhibitors of IRAK4 of Formula I and provides compositions comprising such inhibutors, as well as methods therewith for treating IRAK4-mediated or -associated conditions or diseases.

The present invention relates to inhibitors of IRAK4 of Formula I and provides compositions comprising such inhibutors, as well as methods therewith for treating IRAK4-mediated or -associated conditions or diseases.

The present invention relates to (R)-9-(2,5-difluorophenethyl)-4-ethyl-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one salts, to pharmaceutical compositions comprising them, and to their use in therapy and/or prophylaxis of sigma receptor and/or μ-opioid receptor associated disease.

Benzimidazoles of formula (I): wherein: A is 5- to 12-membered aryl or 5- to 12-membered heteroaryl, each of which is unsubstituted or substituted; Y is a single bond, —(CH.sub.2).sub.p—, —X—, —CH.sub.2—X—, or —X—CH.sub.2—; X is —O—, —S—, —N(R.sup.2)—, >C═O, >S(═O), >S(═O).sub.2, —O—C(═O)—, —C(═O)—O—, N(R.sup.2)—C(═O)—, or —C(═O)—N(R.sup.2)—; each L is independently a single bond, C.sub.1-3alkylene, C.sub.2-3alkenylene or C.sub.2-3alkynylene; R.sup.1 is C.sub.1-6alkyl, C.sub.2-6alkenyl or C.sub.2-6alkynyl, each of which is unsubstituted or substituted; each Z is independently —N(R.sup.2).sub.2, —OR.sup.2, —SR.sup.2, —S(═O)R.sup.2, —S(═O).sub.2R.sup.2; each R.sup.2 is independently hydrogen, C.sub.1-6alkyl, C.sub.2-6alkenyl or C.sub.2-6 alkynyl, wherein said alkyl, alkenyl and alkynyl groups are unsubstituted or substituted; m is 0, 1, 2, or 3; n is 1, 2, or 3; and p is 1, 2, or 3; and the pharmaceutically acceptable salt thereof are inhibitors of RSV and can therefore be used to treat or prevent an RSV infection. ##STR00001##

Benzimidazoles of formula (I): wherein: A is 5- to 12-membered aryl or 5- to 12-membered heteroaryl, each of which is unsubstituted or substituted; Y is a single bond, —(CH.sub.2).sub.p—, —X—, —CH.sub.2—X—, or —X—CH.sub.2—; X is —O—, —S—, —N(R.sup.2)—, >C═O, >S(═O), >S(═O).sub.2, —O—C(═O)—, —C(═O)—O—, N(R.sup.2)—C(═O)—, or —C(═O)—N(R.sup.2)—; each L is independently a single bond, C.sub.1-3alkylene, C.sub.2-3alkenylene or C.sub.2-3alkynylene; R.sup.1 is C.sub.1-6alkyl, C.sub.2-6alkenyl or C.sub.2-6alkynyl, each of which is unsubstituted or substituted; each Z is independently —N(R.sup.2).sub.2, —OR.sup.2, —SR.sup.2, —S(═O)R.sup.2, —S(═O).sub.2R.sup.2; each R.sup.2 is independently hydrogen, C.sub.1-6alkyl, C.sub.2-6alkenyl or C.sub.2-6 alkynyl, wherein said alkyl, alkenyl and alkynyl groups are unsubstituted or substituted; m is 0, 1, 2, or 3; n is 1, 2, or 3; and p is 1, 2, or 3; and the pharmaceutically acceptable salt thereof are inhibitors of RSV and can therefore be used to treat or prevent an RSV infection. ##STR00001##

The present invention provides compounds of Formula I ##STR00001##
and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

The present invention provides compounds of Formula I ##STR00001##
and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

The present invention provides compounds of formula (I): compositions comprising such compounds; the use of such compounds in therapy (for example in the treatment or prevention of a disease, disorder or condition ameliorated by inhibition of a dopamine transporter); and methods of treating patients with such compounds; wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.9, R.sup.10, Q, X, Y, Z, A, L, B, m, n and p are as defined herein.

##STR00001##

Disclosed are a compound of formula I as a toll-like receptor 7 (TLR7) agonist or a pharmaceutically acceptable salt thereof for treating colorectal cancer, a pharmaceutical combination for treating colorectal cancer comprising the TLR7 agonist and a tyrosine kinase inhibitor, and the use of the compound of formula I or the pharmaceutically acceptable salt thereof and the pharmaceutical combination for treating colorectal cancer.

##STR00001##